In recent years, the association of cancer aggravation with inflammatory cells and immune cells has been revealed.
A part of the mechanism on metastasis of cancer cells circulated in blood (Circulating Tumor Cells: CTCs) has been reported (Non Patent Literature 1). According to the literature, CTCs are naturally susceptible to the attack by natural killer cells (NK cells) but can avoid the attack by NK cells through attachment of a large number of platelets to the CTCs thereto. Additionally, CTCs in such condition easily adhere to the vascular endothelium, which is then activated when neutrophils are recruited in the proximity of the adhered CTCs, whereby the CTCs extravascularly transmigrate and propagate to give rise to cancer metastasis in the end.
It is also reported that there is a significant correlation between the neutrophil count (N) to lymphocyte count (L) ratio (NLR) in peripheral bloods of cancer patients and the prognosis of the cancer patients and that when the NLR is high, the prognosis is poor (Non Patent Literature 2).
Bestatin (registered trademark) is known to contain, as an active ingredient, (2S)-2-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoylamino]-4-methylpentanoic acid (generic name: Ubenimex), binds to the aminopeptidase present on the surface of immunocompetent cells to exhibit immune reinforcement effects on cancer patients, and is approved by the Japanese authorities for the application of extending the survival time by the combined use with a maintenance and consolidation therapy agent after the remission induction of adult acute non-lymphatic leukemia and has been clinically applied (Non Patent Literature 3). It is further reported that a combination therapy, which is not applicable, has been attempted wherein, although each administration and dose is within the range of approval and authorization, a high dose of Bestatin (30 mg/day) and a high dose of UFT (400 mg/day (divided administration, twice a day)) are administered every day after surgery on bladder cancer patients, and that the combination therapy was useful when compared with UFT single administration groups (Non Patent Literature 4). It is further suggested that Bestatin is useful as a therapeutic agent for cancers with which cancer stem cells are associated, because the aminopeptidase N to which Bestatin binds is the same as the receptor (CD13) relating to the growth of cancer stem cells and the antitumor effect was confirmed when an extremely high dose (20 mg/kg) of Bestatin and a high dose (30 mg/kg) of 5-FU were administered multiple times to mice to which cancer stem cells were transplanted (Patent Literature 1 and Non Patent Literature 5).